BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF.
METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated.
RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002).
CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

OBJECTIVE: Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM) clinical phenotypes. The aim of this study is to explicate the clinical and immunological features of MSAs-negative DM patients.
METHODS: A total of 515 individuals diagnosed with DM was screened from 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed.
RESULTS: MSAs-negative DM patients were categorized into two groups: MAAs-negative (MSAs (-)/MAAs (-)) group and MAAs-positive (MSAs (-)/MAAs (+)) group. The percentage of Raynaud\'s phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positive DM patients and MSAs (-)/MAAs (-) DM patients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumonia and usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among total CD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onset age, higher level of carcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients.
CONCLUSIONS: Compared with MSAs-positive group, MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DM patients:   • The MSAs (-)/MAAs (+) DM patients demonstrated a higher prevalence of organizing pneumonia (OP) and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid.   • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients.   • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negative patients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients.   • MSAs-negative DM patients had a more favorable prognosis than MSAs-positive DM patients. A multivariable regression analysis revealed the advanced onset age, high CEA levels, and RP-ILD were risk factors for mortality in DM patients.

Background Previous studies have demonstrated dexamethasone (DEX)\'s efficacy for coronavirus disease 2019 (COVID-19). In contrast, patients with residual lung field shading and symptoms after DEX treatment have been observed, and the efficacy of additional corticosteroids (AC) is unknown. Objectives We aimed to investigate the efficacy of AC in patients with COVID-19 with residual respiratory symptoms or who required oxygen therapy or invasive mechanical ventilation after DEX treatment. Methods This was a single-center, retrospective observational study including 261 patients with community-onset COVID-19, aged ≥ 18 years, admitted to our hospital between March 1, 2020, and May 31, 2021. Finally, 34 patients were included in the study who met all four of the following criteria: (1) required oxygen therapy or invasive ventilation, (2) were treated with DEX, (3) had residual shading on chest imaging after DEX treatment, or (4) had unimproved respiratory symptoms or oxygen saturation < 90%. We reviewed the medical records and clinical courses of 14 patients who received AC therapy (AC group) and 20 patients who did not (non-additional corticosteroids or NC group). Results The 90-day mortality rate was 35.7% in the AC group and 25.0% in the NC group. There was no statistically significant difference between the two groups (p = 0.797). In addition, there was no difference between groups in the proportion of patients who required oxygen therapy at discharge (64% vs. 35%, p = 0.162). The time from the end of DEX therapy to discharge was significantly longer in the AC group (median 7.5 vs. 33 days, p = 0.019). Regarding serious adverse events, infection was statistically more common in the AC group than in the NC group (p = 0.005). Conclusions AC after DEX treatment does not improve clinical outcomes and may prolong hospital stay.

Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia generally requiring steroid therapy, and spontaneous resolution has been reported in patients with mild disease. However, evidence supporting the need for COP treatment is poor. Therefore, we investigated the characteristics of patients with spontaneous resolution. We retrospectively collected data from 40 adult patients who were diagnosed with COP through bronchoscopic examination at Fukujuji Hospital from May 2016 to June 2022. Sixteen patients who improved without steroid therapy (the spontaneous resolution group) and 24 patients who required steroid therapy (the steroid therapy group) were compared. Patients in the spontaneous resolution group showed a lower C-reactive protein (CRP) concentration (median 0.93 mg/dL [interquartile range [IQR] 0.46-1.91] vs median 10.42 mg/dL [4.82-16.7], P < .001), a higher lymphocyte ratio (median 21.7% [18.2-25.2] vs median 13.3% [8.8-19.8], P = .002), and a longer duration from symptom onset to diagnosis of COP (median 51.5 days [24.5-65.3] vs 23.0 days [17.3-31.8], P = .009) than those in the steroid therapy group. Within 2 weeks, all patients in the spontaneous resolution group showed relief of symptoms and alleviated radiographic findings. The area under the receiver operating characteristic (ROC) curve was 0.859 (95% confidence interval [CI]: 0.741-0.978) in CRP. When we arbitrarily determined the cutoff values, including CRP levels of ≤3.79 mg/dL, the sensitivity, specificity, and odds ratio were 73.9%, 93.8%, and 39.8 (95% confidence interval: 4.51-1968.9), respectively. Only 1 patient in the spontaneous resolution group showed recurrence but did not require steroid therapy. Conversely, 4 patients in the steroid therapy group showed recurrence and were treated by an additional course of steroids. The characteristics of COP with spontaneous resolution and factors that determine the patients in whom steroid therapy might be avoided is detailed in this study.

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.

Rationale: The natural history of recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unknown. Because fibrosis with persistent physiological deficit is a previously described feature of patients recovering from similar coronaviruses, treatment represents an early opportunity to modify the disease course, potentially preventing irreversible impairment.Objectives: Determine the incidence of and describe the progression of persistent inflammatory interstitial lung disease (ILD) following SARS-CoV-2 when treated with prednisolone.Methods: A structured assessment protocol screened for sequelae of SARS-CoV-2 pneumonitis. Eight hundred thirty-seven patients were assessed by telephone 4 weeks after discharge. Those with ongoing symptoms had outpatient assessment at 6 weeks. Thirty patients diagnosed with persistent interstitial lung changes at a multidisciplinary team meeting were reviewed in the interstitial lung disease service and offered treatment. These patients had persistent, nonimproving symptoms.Results: At 4 weeks after discharge, 39% of patients reported ongoing symptoms (325/837) and were assessed. Interstitial lung disease, predominantly organizing pneumonia, with significant functional deficit was observed in 35/837 survivors (4.8%). Thirty of these patients received steroid treatment, resulting in a mean relative increase in transfer factor following treatment of 31.6% (standard deviation [SD] ± 27.6, P < 0.001), and forced vital capacity of 9.6% (SD ± 13.0, P = 0.014), with significant symptomatic and radiological improvement.Conclusions: Following SARS-CoV-2 pneumonitis, a cohort of patients are left with both radiological inflammatory lung disease and persistent physiological and functional deficit. Early treatment with corticosteroids was well tolerated and associated with rapid and significant improvement. These preliminary data should inform further study into the natural history and potential treatment for patients with persistent inflammatory ILD following SARS-CoV-2 infection.

BACKGROUND: Pulmonary infiltrates of variable etiology are one of the main reasons for hypoxemic respiratory failure leading to invasive mechanical ventilation. If pulmonary infiltrates remain unexplained or progress despite treatment, the histopathological result of a lung biopsy could have significant impact on change in therapy. Surgical lung biopsy is the commonly used technique, but due to its considerable morbidity and mortality, less invasive bronchoscopic transbronchial lung biopsy (TBLB) may be a valuable alternative.
METHODS: Retrospective, monocentric, observational study in mechanically ventilated, critically ill patients, subjected to TBLB due to unexplained pulmonary infiltrates in the period January 2014 to July 2019. Patients\' medical records were reviewed to obtain data on baseline clinical characteristics, modality and adverse events (AE) of the TBLB, and impact of the histopathological results on treatment decisions. A multivariable binary logistic regression analysis was performed to identify predictors of AE and hospital mortality, and survival curves were generated using the Kaplan-Meier method.
RESULTS: Forty-two patients with in total 42 TBLB procedures after a median of 12 days of mechanical ventilation were analyzed, of which 16.7% were immunosuppressed, but there was no patient with prior lung transplantation. Diagnostic yield of TBLB was 88.1%, with AE occurring in 11.9% (most common pneumothorax and minor bleeding). 92.9% of the procedures were performed as a forceps biopsy, with organizing pneumonia (OP) as the most common histological diagnosis (54.8%). Variables independently associated with hospital mortality were age (odds ratio 1.070, 95%CI 1.006-1.138; p = 0.031) and the presence of OP (0.182, [0.036-0.926]; p = 0.040), the latter being confirmed in the survival analysis (log-rank p = 0.040). In contrast, a change in therapy based on histopathology alone occurred in 40.5%, and there was no evidence of improved survival in those patients.
CONCLUSIONS: Transbronchial lung biopsy remains a valuable alternative to surgical lung biopsy in mechanically ventilated critically ill patients. However, the high diagnostic yield must be weighed against potential adverse events and limited consequence of the histopathological result regarding treatment decisions in such patients.

Cicatricial organizing pneumonia (CiOP) refers to intraluminal collagen deposition in a background of otherwise classic appearing organizing pneumonia (OP), sometimes with formation of peculiar fibrous nodules or densely fibrotic linear bands. Dendriform ossification has been also described in CiOP cases. This study is to evaluate the clinicopathologic and radiologic characteristics of CiOP identified in a cohort of OP cases diagnosed by surgical lung biopsy at a single institution. Electronic search was performed to find surgical lung biopsy cases with OP as the main histopathologic diagnosis during a 9-year period (2005-2013). The presence of mature collagen deposition in intraluminal plugs of OP (Masson bodies), linear fibrous bands, and ossification in association with OP was evaluated. Pertinent clinical information was obtained from medical records, and available chest computed tomography (CT) scans were reviewed by a chest radiologist. A total of 56 cases met the study criteria. Thirty-two of 56 cases (57.1%) showed at least 10% of cicatricial element within Masson bodies, 9 of which revealed cicatricial elements comprising 50% or higher proportion of OP. All 9 cases with CiOP as the major component (≥50%) revealed some areas of linear fibrous bands. Five of these 9 cases had intraluminal ossification, with features suggestive of dendriform ossification. Twenty of 32 cases with the cicatricial component had postoperative follow-up CT scans ranging from 0.4 to 171 months (median = 44) after the biopsy; 18 of these 20 cases showed stable finding or resolution of radiologic densities. Six of 9 patients with CiOP with major cicatricial change (≥50%) were alive and well at the time of clinical follow-up (median = 47 months; range = 12-125). In summary, minor cicatricial changes involving Masson bodies were seen in more than half of our OP cases, and patients with CiOP seem to follow an indolent and favorable course on radiologic and clinical follow-up, even in those with major cicatricial changes (≥50%) that were often accompanied by linear fibrous bands and/or intraluminal ossification.

BACKGROUND: Organizing pneumonia (OP) is a rare disease that is often easily misdiagnosed as a malignancy. The diagnosis of OP can prove quite challenging. Patients typically receive treatment with high-dose corticosteroids. Relapse is common if corticosteroid treatment is reduced or stopped. However, given that long-term corticosteroid treatment often results in significant side-effects, the aim of this study was to discuss the diagnosis and surgical treatment of OP.
METHODS: The medical records of 24 patients with pathologically diagnosed OP between October 2007 and January 2019 were retrospectively reviewed. All patients underwent thoracic computed tomography (CT) and transbronchial biopsy or CT-guided percutaneous needle aspiration. We analysed the clinical manifestations, radiological findings, diagnostic methods, treatment, and follow-up outcomes of all patients.
RESULTS: In total, 24 patients with OP were identified. The study included 17 (70.8%) men and 7 (29.2%) women, and the mean age was 61.25 ± 11.33 years (range: 31-82). The most common symptom was cough (n = 16; 66.6%), and the most common radiological finding was consolidation (n = 13; 54.2%) on thoracic CT. The diagnosis of OP was made by transbronchial biopsy in 11 patients (45.8%), and percutaneous needle aspiration biopsy in 13 (54.2%). We performed 11 wedge resections, 9 segmentectomy, and 4 lobectomies. Twenty patients underwent video-assisted thoracoscopic surgery (VATS), and 4 underwent thoracotomy. Complete lesion resection was obtained in all patients, and all patients were discharged from the hospital between 5 and 11 days after surgery. The mean follow-up period was 59.1 ± 34.5 (range: 2-134) months. Residual lesions or local or distant recurrence were not observed.
CONCLUSIONS: OP is a rare disease, and the exact aetiology remains unclear. Preoperative diagnosis is difficult to achieve despite the use of transbronchial biopsy or CT-guided percutaneous needle aspiration. Complete surgical resection represents an effective method for the treatment of OP.